Alpha-adrenergic control of serotonin release from rat pineal glands.

This study was designed to determine if norepinephrine (NE) stimulated release of pineal serotonin (5-HT) is receptor mediated and to identify the receptor(s) most influential in the release process. Efflux of 3H-5-HT from rat pineals in vitro was significantly increased within 5 min after NE was added to perifusion buffer in concentrations ranging from 0.1 to 3 microM. 3H-5-HT was not simply displaced from pinealocytes by NE, since buffer containing 3 microM 5-HT had no effect on 3H-5-HT efflux. Furthermore, NE enhanced 3H-5-HT secretion by a stereospecific process, since d-NE was significantly less effective than l-NE. The alpha 1-adrenoreceptor agonists phenylephrine and cirazoline simulated the effects of NE, significantly increasing 3H-5-HT efflux in single and sequential stimulations. Furthermore, the alpha 1-adrenergic receptor antagonist prazosin reduced NE-stimulated release of 3H-5-HT. In contrast, the alpha 2- and beta-adrenoreceptor agonists naphazoline or clonidine and isoproterenol, respectively, were without effect. In addition, the alpha 2- and the beta-receptor antagonists rauwolscine and timolol, respectively, had no effect on NE-stimulated release of pineal 5-HT. In conclusion, the data show that NE stimulates 5-HT release within minutes from rat pineal glands in vitro. Unlike the pineal mechanism controlling melatonin synthesis, which has a longer latency and requires beta-adrenergic receptor activation, 5-HT release is regulated by activation of alpha 1-receptors. Thus, the pineal may be useful model for studying how separate intracellular processes are controlled by common neural stimuli.